How Caloric Restriction and NAD+ Can Lengthen Your Lifespan

Nicotinamide adenine dinucleotide (NAD+) is a molecule essential in every single one of the 37 trillion cells of the body. It has hundreds of functions, including helping to support energy metabolism and regulating essential cellular processes. In fact, the role of NAD is so crucial in cellular processes that without it, life would not be possible (1).

One of the key factors in aging is reductions in intracellular NAD+ levels. Increasing NAD+ levels helps to prevent age-related deterioration of the body. With reduced NAD+ levels, we also see slowed cellular function, contributing to the development of numerous age-related diseases like heart disease and Alzheimer's disease, among numerous others (2).

While there are several cutting-edge NAD+ supplementations and therapeutic options that can increase intracellular NAD+ concentrations, there are also ways to naturally increase NAD+, such as exercise, food choices, and, this article's topic, caloric restriction.

It may seem counter-intuitive, but recent research shows that caloric restriction may be a pivotal element to unlocking a more extended lifespan through activating DNA renewal, a process for which NAD+ is essential. 

What is Caloric Restriction?

There isn't a unified definition of calorie restriction. Generally speaking, however, it refers to up to anywhere between a 10% 50% reduction of calories from a regular diet (3, 4). Calorie restriction does not refer to simply ensuring you do not overeat but to limiting caloric intake to consume significantly fewer calories than your body needs to maintain standard metabolic pathways (5).

When you restrict calorie intake, your body begins to seek out alternative energy sources. First, it will seek out the glucose stored in the liver and the muscles, and then it will turn to breaking down fat and, potentially, protein from muscle. Which source your body uses depends on the quality of the diet and the levels of physical activity, among others (5).

The Connection Between Caloric Restriction, Longevity, and NAD+ Levels

  A review of research revealed that several studies have demonstrated or suggested that caloric restriction helps to improve not only lifespan but healthspan, or the number of healthy years in a person's life. In several animal species and microorganisms, caloric restriction alone has significantly increased lifespan (4, 6). Finding included the following (7):

-    Caloric restriction helps to improve motor coordination locomotor activity, enhances memory, reduces performance defects, and delays motor neuron death in animal studies.

-   Caloric restriction counteracts the hallmarks of cellular aging, including genomic instability, telomere erosion, epigenetic alteration, impaired nutrient sensing, cellular aging and dysfunction, stem cell depletion, and abnormal intracellular communication, among others.

-   Caloric restriction delays the onset or improves the prognosis of age-related diseases by modulating the pathways of sirtuins, a family of proteins that depend on NAD+.

While caloric restriction on its own likely has beneficial effects for lifespan, human studies show that caloric restriction combined with supplementation with nicotinamide riboside (NR) a NAD+ precursor, may magnify the benefits of caloric restriction on its own. To cite a recent study, "Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate for enzymes involved in the beneficial [cardiovascular] effects of regular calorie restriction on healthspan." (8)   Caloric restriction and NAD+ precursor supplementation independently improve NAD+ levels. When implemented together the effects may be magnified (8, 9).

Can Caloric Restriction Be Coupled with Physical Activity?

  Caloric restriction may be coupled with physical activity when the physical activity remains light to moderate and focuses primarily on cardiovascular activity rather than weight-training or high-intensity activity (10).

When individuals restrict caloric intake, their body shifts metabolic pathways away from breaking down glucose to breaking down fat cells. This causes the body to enter a state of ketosis, which is normal and one factor that influences the benefits of caloric restriction. However, increasing the demand for energy while having too much caloric deficit could trigger ketoacidosis, especially if the individual has dysfunctional metabolic pathways (11).

However, coupling caloric restriction with moderate movement throughout the day can help the body eliminate toxins and waste. Since caloric restriction incites autophagy, or the killing of older, dysfunctional cells to make way for new ones, movement helps to activate routes of toxin elimination (12).

A Note From Our Expert

While there is promising initial clinical evidence about the role of caloric restriction in human health, there are inconsistent study results due mainly to differences in study designs. In the coming years, we will likely have much more clarity regarding the impact of caloric restriction on human health and longevity.

If you are thinking of restricting caloric intake or combining caloric restriction with physical activity, our in-house expert has direct experience with clients aiming to improve healthspan and overall wellness.

Longevity Collective's own expert, Jeanne Pitre, describes how coupling movement and light to moderate cardio with caloric restriction has helped to optimize brain function and overall wellbeing.

Jeanne Pitre, describes what has worked for her was people do better with caloric restriction and the induction of autophagy when they are in their body. Do it for optimizing brain function and

increasing overall wellness. She recommends low-impact cardiovascular activities like water aerobics, walking, light jogging. 

1.     Chini, C. C., Tarragó, M. G., & Chini, E. N. (2017). NAD and the aging process: Role in life, death and everything in between. Molecular and Cellular Endocrinology, 455, 62–74. https://doi.org/10.1016/j.mce.2016.11.003

2.     Hong, W., Mo, F., Zhang, Z., Huang, M., & Wei, X. (2020). Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.00246

3.     Bales, C. W., & Kraus, W. E. (2013). Caloric Restriction. Journal of Cardiopulmonary Rehabilitation and Prevention, 33(4), 201–208. https://doi.org/10.1097/hcr.0b013e318295019e

4.     Grabski, I. (2020, August 2). Can Calorie Restriction Extend Your Lifespan? Science in the News. https://sitn.hms.harvard.edu/flash/2020/can-calorie-restriction-extend-your-lifespan/  

5.     Ottinger, M. A. (2018). A Comparative Approach to Metabolic Aspects of Aging: Conserved Mechanisms and Effects of Calorie Restriction and Environment. Progress in Molecular Biology and Translational Science, 109–127. https://doi.org/10.1016/bs.pmbts.2017.11.004  

6.     Evans, C., Bogan, K. L., Song, P., Burant, C. F., Kennedy, R. T., & Brenner, C. (2010). NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity. BMC Chemical Biology, 10(1). https://doi.org/10.1186/1472-6769-10-2

7.     Michan, S. (2014). Calorie restriction and NAD+/sirtuin counteract the hallmarks of aging. Frontiers in Bioscience, 19(8), 1300. https://doi.org/10.2741/4283

8.     Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-03421-7

9.     Imai, S. I., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology, 24(8), 464–471. https://doi.org/10.1016/j.tcb.2014.04.002

10.  Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012). Of mice and men: The benefits of caloric restriction, exercise, and mimetics. Ageing Research Reviews, 11(3), 390–398. https://doi.org/10.1016/j.arr.2011.11.005

11.  Cooper, J. N., Columbus, M. L., Shields, K. J., Asubonteng, J., Meyer, M. L., Sutton-Tyrrell, K., Goodpaster, B. H., DeLany, J. P., Jakicic, J. M., & Barinas-Mitchell, E. (2012). Effects of an intensive behavioral weight loss intervention consisting of caloric restriction with or without physical activity on common carotid artery remodeling in severely obese adults. Metabolism, 61(11), 1589–1597. https://doi.org/10.1016/j.metabol.2012.04.012

12.  Green, D. R., Galluzzi, L., & Kroemer, G. (2011). Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging. Science, 333(6046), 1109–1112. https://doi.org/10.1126/science.1201940